The bleomycins are a family of antitumor antibiotics used for the treatment of squamous cells carcinomas and malignant lymphomas. Although clinically effective, various bleomycins have exhibited pulmonary, renal and CNS toxicities; the identification of potentially more efficacious bleomycin analogy is the long-term objective of this proposal. For the five year period of requested support, we propose to syntesize the bleomycin group antibiotic tallysomycin, which is known to have an altered profile of antitumor activity in animal models. Also proposed for synthesis are bleomycin congeners and "fragments" that can help to define . the structural features in BLM conducive to efficient DNA unwinding . BLM congeners resistant to self-inactivation . the structural / reactive nature of activated BLM